J.C.S. CHEM. COMM.

, 1980 219
Copper(1) Complex -catalysed Reduction of Dioxygen to Water and
Oxidation of Alcohols : a Model of Copper(1) -containing Oxidase
By MEGUMU MUNAKATA, SHIGERU NISHIBAYASHI, and HIROMASA SAKAMOTO
(Departnzent of Chemastry, Kznkz Unzverszty, Kowakae, Hzgasliz-Osaka, Osaka 577, Japan)
Surnnzary Binary copper(1) complexes with 2,2-bipyricline,
4,4-dimethyl-2,2-bipyridine, 2,2,2-terpyridine, and
ethylenedianiine and ternary copper ( I ) complexes con-
taining 2,2-bipyridine and P-diketonates catalyse the
reduction of 0, to H,O and the oxidation of primary and
secondary alcohols to aldehydes and ketones, respectively
COPPER proteins are metalloenzymes which play an im-
portant role in oxidation-reduction, oxygenation, and
oxygen carrying Most of the proteins contain copper(I1)
ions Tyrosinase is a typical copper(1) -containing protein
and catalyses both the reduction of 0, to H,O and the
reduction of one atom of 0, to H,0 with hydroxylation of
the other atom Few copper(1) complexes having enzyme-
like activity have been reported , Me report here some
copper(1) complexes which cdtalyse the reduction of 0, to
H,O together with oxidation of alcohols, z e , a inodel of
copper(1) -containing oxidase, and our studies on the
reaction mechanism The copper(1) complexes were ob-
tained in two forms a, as the chlorides [CuL,]Cl, and b, as
the mixed ligand complexes Cu(L)A To obtain the
complexes [CuL,]CI copper(1) chloride crystals were added
to alcoholic solutions of the ligands (L) under S, in the mole
ratio 1 : 2 and after 3 h stirring the copper(1) complexes,
[CuL,]Cl, were formed quantitatively I n the preparation
of the mixed ligand coppei(1) complexes, Cu(L)A, the mole
ratio of CuCl : I,: A used was 1 : 1 : 1, where L is 2,2-bipv-
ridine( bpy) , 4,4-diniethyl-2,2-bipq-ridine (4,4-Me,-bpy),
and ethylenediamine (en) ant1 A is lithium acetylacetonate
(Li-acac) and lithium thenoyltrifluoroacetonate (Li-tta)
Dioxygen was passed into alcoholic solutions of [CuL,J CI
and Cu(L)A to give ketones or aldehydes as products, as
confirmed by g 1 c The products could also be precipitated
as their 2,4-dinitrophenylhydrazones which were then iden-
tified by i r spectroscopy and satisfactory elementary
analyses The quantity of water produced in the oxidation
was determined by Karl-Fischer titration
TABLE Acetaldehyde formed on copper(r) complex-catalysed
oxidation of ethanol a
Acetaldehyde/ 1 0-3~f
36
28
15
10
5. 3
1.5
Not detected
Not detected
Not detected
Not detected
Not detected
Not detected
a Flow rate of 0, : 190 nil ~nin-
M
b Concentration of copper(1)
complex in ethanol =5 x
The Table shows the concentration of acetaldehyde
formed from the copper ( I ) complex-catalysed oxidation of
ethanol under 0, for 1 h at 15 C The catalysis of [Cu-
(4,4-Me,-bpy),]Cl (1) and [Cu(bpy),]Cl (2) is large com-
pared to that of [Cu(tpy)Cl]C1(3) [(tpy)Cl =2,2,2-terpyri-
dine] and [Cu(en),]Cl which are easily oxidized to the
corresponding copper(I1) complexes Coniplexes (1) and (2)
are very slowly oxidized to the corresponding copper(r1)
conipleves and show no catalytic activity after ca 10 h
reaction under the oxygenation conditions Copper(I1)
complexes such as [Cu(bpy),]Cl,, [Cu(tpy)Cl]Cl, [Cu(bpy)-
(acac)]CI, and [Cu(4,4-il.le2-bpy),]C1, do not catalyse the
oxidation Also [Cu(pheiz),]Cl (4), [Cu(5-X02-phen),]C1
( 5) , [Cu(5-Cl-phen),]CI (6), [Cu(2,9--Me,-phen),]Cl (7), and
[Cu(biq),]CI ( 8) , the copper(1) states hich are more stable
than those of (1) and (2), show no catalysis (phen, acac, and
biq are 1,10-phenanthroline, acetylacetonate, and 2 , Y-
biquinoline, respectively) Since (1) md (2) possess
appropriate redox potentials for this oxidation (CuI/CuII),
catalysis may be extensive This is supported by the redox
potentials of (1) ( +91 mV) and (2) (+ 120 m\ ) being
between those of (3) (- 80 mV) and (4) (+ 174 mV) The
dependence of the catalytic activity of the copper(r)
complexes on their redox potentials suggests the formation
of the 0,-adduct of the complex as an intermediate * This
is supported by the fact that exposure of the reddish brown
ternary copper( I ) complexes in alcoholic solution to oxygen
yields a pale blue species and the solution is reconverted
into the reddish brown form bv deaeration with N, for 3 11
Tormation of the 0,-adduct of (2) has been suggested by a
hinetic study on the oxidation of (2) in aqueous solution
Another important factor in the catalysis is the flexibility
of the copper(1) complexes 1 he CuI complex which has a
tetrahedron structure must change to a five-co-orclinated
structure in order to combine with dioxygen The steric
barrier to the conformational change of (1) and (2) IS
smaller than that for Cu(4,7-Me2-phen),C1 (9), since the
2,2-bipvridine skeleton, in which the two pyridine groups
are bound by a single bond, is more flexible than the
1,10-phenanthrohne sheletoii (i Therefore, (9) does not
combine with 0, and shows no catalytic properties though
its oxidation potential is between that of (1) and (2) 7 The
mole ratio of aldehyde/water produced in the oxidation c.f
ethanol and propan-1-01 is 1 Primary alcohols are not
oxidized to carboxylic acids in the catalysis The mole
ratios of ketone/water obtained for the oxidation of
propan-2-01 and butan-2-01 were ca 0.9 and 0 8, respectively
If the copper(1) complexes catalysed a four-electron transfer
converting 1 niol of 0, into 2 mol of H,O during the oxida-
tion of 2 mol of alcohol to 2 mol of the corresponding
aldehyde or ketone (Scheme l), the mole ratio of the
aldehyde or ketone to water should be 1: 1 Therefore,
the mole ratio obtained for the oxidation of the secondary
alcohols cannot be explained by Scheme 1
t Redox potentials (CuII/CuI) of (1) (2), and (9) in 50% dioxan-water are 204, 251, and 220 mV, respectively (see ref 3)
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220 J.C.S. CHEM. COMM., 1980
CU ~ o r n p ~ e x ~ ~ - adduct
2 R-,
2 R--%
R/-CH-oH
F Y C =O + 2Hzo
SCHEME 1
We found that copper(1) complexes also catalyse the
reduction of H,O, to H,O during the oxidation of primary
and secondary alcohols. In the oxidation of ethanol and
propan- 1-01 the quantity of aldehyde obtained was equal to
the amount of H202 added but in the oxidation of propan-
2-01 and butan-2-01 less ketone was obtained giving acetone
and ethyl methyl ketone in 75 and 50% yield, respectively.
H20, in alcohols with a lower dielectric constant may be
partially decomposed to H,O and 0, by the copper(1)
complexes. This suggests the mechanism shown in
Scheme 2 for copper(r) complex-catalysed oxidations of
alcohols, as i t explains the difference in the mole ratio of the
oxidation product to water. The possibility of formation
of H20, with the reduction of the 0,-adduct of (2) in aqueous
solutions has been reported .5 Copper(1) complexes also
catalyse the oxidation of catechol and etliane- 1,2-diol.
Tyrosinase, which has 4 g atoms of copper(1) per mole,
catalyses the reduction of 0, to H20. Those copper(1)
complexes which catalyse this reduction are thus models of
9 2
Cucomplex 0 - adduct
R
R/_--CHOH
\
R. =
I
,-C=O +H202
R
c I c 0 m pl ex ~~~ Ho
Rf,c=o
2H20
SCHEME 2
tyrosinase although in a two-step reduction (0, to H,O, then
H,O, to H20) and the turnover numbers ( <042) are
very small.
I n conclusion the catalytic activity of copper(1) com-
plexes depends upon their redox potentials and flexibility
which govern the formation of 0,-adducts of the com-
plexes. Work on the copper( I ) complex-catalysed oxygena-
tion of monophenols, the oxidation of o-diphenols, and the
structure of the 0,-adduct is in progress.
(Received, 30th Ociaber 1979; Corn. 1158.)
The Biochemistry of Copper, ed. J . Peisach, P. Aisen, and W. E. Blumberg, Academic Press, New York, 1966; Inorganic Bio-
chemistry, ed. G. L. Eichhorn, Elsevier, Amsterdam, 1973 ; Bioinorganic Chemistry-11, ed. K. N. Raymond, American Chemical
Society, Washington D.C., 1977.
J . Tsuji and H. Takayanagi, J . Amev. Chem. Soc., 1974, 96, 7349; J . Tsuji, H. Takayanagi, and I. Sakai, Tetvahedron Letters,
1975, 1245.
B. R. J ames, and R. J . P. Williams, J . Chem. Soc., 1961, 2007: the redox potentials of (5)-(8) are more positive than that of (4).
A. E. Martell and M. Calvin, Chemistry of the Metal Chelate Compounds, Prentice-Hall, New J ersey, 1956, p. 350.
I. Pecht and M. Anbar, J . Chem. SOG. ( A) , 1968, 1902.
1,lO-Phenanthroline is rigidly held in a czs-conformation, and is almost always found as a planar ligand, see J . V. Rund, Inorg.
Chem., 1968, 7, 24.
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